Venom Extracts
The biological activity of the crude extracts of the venom of stinging insects has been investigated for well over the last hundred years. Indeed, the first venom of ant to be partially chemically characterized was done so in the 17th century. In that study formic acid was distilled from the ants Formica rufa. Treatment regimes utilizing crude venom extracts (e.g., bee venom), have been reported for the treatment of rheumatoid arthritis. Bee venom has been reported for a treatment of rheumatism in United Kingdom Patent 425,543 issued Mar. 30, 1935; U.S. Pat. No. 2,112,828 issued Aug. 5, 1938 and U.S. Pat. No. 2,154,934 issued Apr. 18, 1939. Typically, however, these treatments have failed to produce noticeable or consistent effects due to the lack of purity of the venom extract and the lack of reproducibility of the venom extract compositions. In addition, since individual insects typically have small amounts of venom present the treatment regimes utilizing venom extracts were prohibitively expensive.
The biological activity of ant species has also been reported in the literature. However, since it is reported that there are over 7600 worldwide species of ants, which comprise at least nine subfamilies within the family formicidae, most ant venoms have not been characterized or isolated. The ant venoms which have been characterized have typically been partially characterized or purified. Indeed, the fact that ants typically possess less than 10 .mu.g of venom per individual has posed a practical problem for obtaining ant venom in reasonable quantity and purity for biochemical or clinical studies and therefore has been partially responsible for the lack of information concerning ant venoms.
A wide variety of proteins, peptides and fairly volatile organic compounds have been reported as being present in ant venom. The proportions of these components is known to vary between species of ants. For instance, the venom of fire ants (Solenopsis invicta and S. richteri) consists predominantly of piperidine alkaloids. The S. invicta fire ant (the red fire ant) contains a much higher percentage of a particular type of alkaloid then do the native North American fire ants. Fire ant venom also contains small quantities of proteins. In contrast, it is reported that the african Solenopsis, S. pinctaticipes venom incorporates an alkaloid composition completely different from those found in the new world fire ants. The sting produced by the venom of this species of ant has a much milder effect on a human than that of the red fire ant.
It is also reported that other ant venoms contain nitrogenous compounds. Other species of ants have been reported to include turpines in their venoms. In addition there is reported to be a wide variety of venoms the bulk of which is comprised of a variety of uncharacterized proteins. For instance, australian Bull Dog ants, Myrmecia pyriformis and M. gulosa, are reported to have significant pharmacological activity. The venoms of these ants contain histamine, phospholipase A, and peptide fractions (responsible for smooth muscle stimulating), hemolytic factors and histamine-releasing activities. Other subspecies of Bull Dog ant venom are reported to contain different proteinaceous venom components which result in different biological effects upon a human. The venom of the New World harvester ant, Pogonomyrmex badius, has been reported to possess at least four different enzymes: hyaluronidase, phospholipase A, acid phosphatase, and esterase.
In light of the above, it is not surprising that the in vivo activity of these crude ant venoms extract would be quite varied. Clearly, many of the in vivo effects of an ant sting or venom extract application to a human would be negative and would, in many cases, be extremely painful and uncomfortable. Indeed, it has been reported that ant stings are capable of causing anaphylaxis in humans and neurotoxic symptoms in mammals.
Crude preparations of ant venoms have, however, been utilized in attempts to treat human ailments such as rheumatoid arthritis; Schultz, D. R. et al, Clinical Research 26 (1), 1978; Schultz, D. R. et al, the Journal of Immunology, 126, 1994-1998 (1981). In addition, the effect on the complement pathway in human serum by polysaccharides from the venom of the tropical ant Pseudomyrmex have also been studied; Dieminger, L. et al, The Journal of Immunology, 123 (5) 1979. Polysaccharides in Pseudomyrmex ant venom have also been isolated and characterized; Schultz, D. R. et al, Molecular Immunology, 16, 253-264, 1979. It has also been reported that crude preparations of ant venom from Pseudomyrmex species have been utilized and shown to have some effect in treating some symptoms of rheumatoid arthritis; Altman, R. D. et al, Arthritis and Rheumatism, 26, (4 suppl.) page S55, 1983; Altman, R. D. et al, Arthritis and Rheumatism, 27, 3 (1984). However, only limited improvements were shown to be as a result of introduction of these crude preparations in an in vivo study. It was reported that 60% of the venom treated patients demonstrated minimal disease activity at the end of a 6 month follow-up, while 40% of the venom treated patients had minimal or no great benefit. It was also reported that response to the venom was not complete in all parameters and that several measurements of active disease failed to demonstrate significant improvement or reduction i.e., walking time, grip strength, ESR, rheumatoid factor and the consumption of nonsteroidal anti-inflammatory drugs. It was also reported that a Pseudomyrmex crude ant venom filtrate contained a factor which was an active anti-inflammatory agent and which apparently had a molecular weight of 1000 or less. This material was said to be not inflammatory and caused the functional inactivation of C3 in normal human serum in vitro; Byrnes, J. J. et al, Clinical Research, Vol. 33, No.2, 1985. Finally, it has also been reported that a purified polysaccharide from Pseudomyrmex has activity as a anti-rheumatoidal agent. U.S. Pat. No. 4,247,540, issued Jan. 27, 1981.